%0 Journal Article
%T A Cre-deleter specific for embryo-derived brain macrophages reveals distinct features of microglia and border macrophages.
%A Brioschi S
%A Belk JA
%A Peng V
%A Molgora M
%A Rodrigues PF
%A Nguyen KM
%A Wang S
%A Du S
%A Wang WL
%A Grajales-Reyes GE
%A Ponce JM
%A Yuede CM
%A Li Q
%A Baer JM
%A DeNardo DG
%A Gilfillan S
%A Cella M
%A Satpathy AT
%A Colonna M
%J Immunity
%V 56
%N 5
%D 05 2023 9
%M 36791722
%F 43.474
%R 10.1016/j.immuni.2023.01.028
%X Genetic tools to target microglia specifically and efficiently from the early stages of embryonic development are lacking. We generated a constitutive Cre line controlled by the microglia signature gene Crybb1 that produced nearly complete recombination in embryonic brain macrophages (microglia and border-associated macrophages [BAMs]) by the perinatal period, with limited recombination in peripheral myeloid cells. Using this tool in combination with Flt3-Cre lineage tracer, single-cell RNA-sequencing analysis, and confocal imaging, we resolved embryonic-derived versus monocyte-derived BAMs in the mouse cortex. Deletion of the transcription factor SMAD4 in microglia and embryonic-derived BAMs using Crybb1-Cre caused a developmental arrest of microglia, which instead acquired a BAM specification signature. By contrast, the development of genuine BAMs remained unaffected. Our results reveal that SMAD4 drives a transcriptional and epigenetic program that is indispensable for the commitment of brain macrophages to the microglia fate and highlight Crybb1-Cre as a tool for targeting embryonic brain macrophages.